Little is known regarding the effect of age on the hepatocyte cellular response in clinical and experimental liver diseases with respect to 1. the mechanisms of liver cell injury and 2. factors important in the repair process. We will employ several in vitro and in vivo model systems to probe the cellular, biochemical, and molecular aspects of the above two fundamentally important areas. We will focus our efforts on the possible cellular mechanisms of hepatocyte injury in clinical liver disease where immunologic phenomena appear important in the pathogenesis and will also study the effect of age on liver damage and repair induced by virus in an experimental animal model. In order to examine the age effect on the hepatocellular repair process, experiments will be performed which emphasize the regulation and control by hormonal agents on hepatocyte proliferation using a recently developed and well characterized primary rat hepatocyte monolayer culture system. Attempts will be made, therefore, to define hormonal influences and other potentially important growth substances on DNA synthesis and hepatic metabolism in the hope of defining changes in hepatocyte cellular responses during the aging process. The tissue culture system allows not only the study and characterization of growth factors but a comparison of response between "young" and "aging" hepatocytes under controlled conditions. This data will provide critical information on the regulation of DNA synthesis and the factors that determine the ability of the hepatocyte to respond to such agents.